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Giulio Maira, Carmelo Anile and Annunziato Mangiola

Object. The primary empty sella syndrome (ESS) represents a heterogeneous clinical picture characterized by endocrine disturbances and signs of intracranial hypertension. An increase in intracranial pressure (ICP) is proposed to be one of the involved pathogenetic factors.

Methods. The series included 142 patients who were observed during a period of 20 years. All patients underwent an ICP and cerebrospinal fluid (CSF) dynamics evaluation through the use of a lumbar constant-rate infusion test.

Impairment of ICP and CSF dynamics was observed in 109 patients (76.8%). In 35 of the 36 patients affected by severe intracranial hypertension without rhinorrhea, improvement in adverse neurological symptoms was achieved after implanting a CSF shunt. Visual function, already seriously compromised before surgery, remained severely altered in one patient. In the group of 34 patients affected by rhinorrhea, CSF leakage was controlled using different surgical treatments: CSF shunt placement in 16 cases, surgical repair of the sellar floor in three, and both procedures in the remaining 13. Two patients refused any surgical treatment.

Conclusions. The role of increased ICP in the pathogenesis and perpetuation of primary ESS has been confirmed. Adverse neurological signs and a CSF leak are correlated with an actual increase in ICP and are relieved after CSF shunt insertion. Cerebrospinal fluid rhinorrhea is more common than generally thought. Its resolution can be achieved using a careful diagnostic protocol and sometimes may require different surgical procedures.

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Eduardo Fernandez, Giulio Maira, Alfredo Puca and Andrea Vignati

✓ The authors present a case of multiple brain metastases and an extracranial secondary localization from malignant melanoma. The patient was operated on three times for the intracranial masses and had a 49-month survival with a good quality of life after the first of the three operations. She lived a total of 80 months from the time of diffusion of the primary tumor. The course of malignant melanoma is unpredictable, and long-term survival can be achieved in some cases, even in the presence of multiple brain metastases.

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Eduardo Fernandez, Roberto Pallini and Giulio Maira

✓ A simple technique is described for protecting the cornea in patients with peripheral facial nerve palsy while waiting for recovery of nerve function. The application of an adhesive strip to the superior eyelid permits opening and closing of the eye, and provides good protection of the cornea.

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Magnetic resonance imaging of intramedullary spinal cord schwannomas

Report of two cases and review of the literature

Cesare Colosimo, Alfonso Cerase, Luca Denaro, Giulio Maira and Romano Greco

✓ Intramedullary spinal cord schwannomas are rare benign tumors for which resection is possible and safe. The purpose of this paper is to present the magnetic resonance (MR) imaging features in two cases of intramedullary spinal cord schwannoma to assist both neurosurgeons and pathologists in preventing misdiagnosis and resultant partial resection. The MR imaging evidence of a small- or medium-sized well-marginated intramedullary spinal cord tumor in a patient in whom no syringomyelia is present but in whom moderate edema with marked Gd enhancement can be seen should be considered in the differential diagnosis of intramedullary spinal cord schwannoma. In cases in which an associated thickened Gd-enhancing spinal nerve root is seen the diagnosis of schwannoma should be assumed.

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Giulio Maira, Luca Denaro, Francesco Doglietto, Annunziato Mangiola and Cesare Colosimo

✓ Idiopathic spinal cord herniation (ISCH) is a rare, although increasingly recognized, cause of myelopathy. It is the result of an anterior dural defect in the thoracic spine through which the spinal cord herniates. Surgical restoration of the herniated cord to its normal position is usually followed by significant improvement in patients' clinical status. Differing surgical techniques have been used to manage the dural defect.

In this report the authors discuss the cases of five patients (four women and one man) with ISCH treated during a 13-year period. Clinical and imaging findings in each patient are reported. Two different surgical techniques were used to treat this condition: dural defect enlargement in two cases and dural patch secured with stitches in three. The intra-and postoperative findings are discussed in relation to the two surgical techniques.

Based on the results and complications in these five cases, the authors now believe that ISCH should be treated, when feasible, by using a dural patch to close the dural defect at the site of the herniation.

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Giulio Maira, Carmelo Anile, Alessio Albanese, Daniel Cabezas, Flaminia Pardi and Andrea Vignati

Object. The optimal approach for the surgical treatment of craniopharyngiomas is still debated. In all cases involving the sella turcica, the authors have exclusively used transsphenoidal surgery (TSS), assuming that this approach is less traumatic than an intracranial one. Moreover, TSS was also performed in some cases of purely suprasellar craniopharyngiomas. In this study the surgical indications and the results obtained in all patients who had undergone TSS were analyzed.

Methods. In a series of 92 patients who underwent surgery for craniopharyngiomas, TSS was the first choice of approach in 57 cases (62%) consisting of 29 female and 28 male patients with ages ranging from 12 to 79 years (mean 35 years). The follow-up duration ranged from 2 to 20 years. A standard transsphenoidal approach was used in patients with an exclusively intrasellar (11 patients) or an intrasellar and suprasellar tumor (37 patients); in nine cases of tumors located exclusively above the sella turcica, a transsphenoidal presellar approach (seven patients) or a transsellar—transdiaphragmatic approach (two patients) was used. Total removal was performed in 36 patients (63%). All patients had good clinical results. Postoperative cerebrospinal fluid leakage occurred in 10 cases, but only one case required a surgical repair of the sella. Two patients died of late complications (3.5%). There were eight cases (14%) of tumor regrowth.

Conclusions. The authors assert that, when used in appropriately located craniopharyngiomas and by neurosurgeons with extensive experience in pituitary surgery, TSS offers excellent results with minor risks.

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Francesco Doglietto, Andrea Bolzoni Villaret, Roberto Stefini, Piero Nicolai, Marco Maria Fontanella, Giorgio Lofrese and Giulio Maira

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Nicola Montano, Quintino Giorgio D'Alessandris, Federico Bianchi, Liverana Lauretti, Francesco Doglietto, Eduardo Fernandez, Giulio Maira and Roberto Pallini

Object

Communicating hydrocephalus is an uncommon complication in patients treated for glioblastoma multiforme (GBM). Its pathogenesis remains unclear. The authors evaluated the clinical and radiological factors associated with the onset of communicating hydrocephalus and the impact of ventriculoperitoneal (VP) shunt surgery on the outcome of these patients.

Methods

One hundred twenty-four patients harboring GBM, who had undergone craniotomy for tumor resection and adjuvant radiochemotherapy, were retrospectively assessed. Seven of them developed communicating hydrocephalus and were treated with VP shunt surgery. Clinical and radiological estimates included Karnofsky Performance Scale (KPS) score, previous surgery, overall survival (OS), CSF pressure and components, tumor location, and leptomeningeal dissemination.

Results

All 7 patients who developed communicating hydrocephalus had undergone at least 2 craniotomies for tumor resection before the onset of hydrocephalus (p = 0.0006; Fisher exact test). Six cases showed high levels of CSF proteins. There was a highly significant relationship between ventricular opening at surgery for tumor recurrence and onset of hydrocephalus (p = 0.0002; Fisher exact test). In these patients, VP shunt surgery was followed by a significant improvement of KPS score (p = 0.0180; Wilcoxon signed-rank test). The median OS after VP shunt insertion was 5 ± 2.9 months.

Conclusions

Ventricular opening after radiochemotherapy and high CSF protein levels are significant predictors of communicating hydrocephalus in patients with GBM. The VP shunt surgery improves quality of life in these patients.

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Lucia Ricci-Vitiani, Francesco Pierconti, Maria Laura Falchetti, Giovanna Petrucci, Giulio Maira, Ruggero De Maria, Luigi Maria Larocca and Roberto Pallini

✓ Permanent cell cultures are invaluable tools for understanding the biological characteristics of tumors. In the present study the authors report on the establishment of permanent human cell lines from three cases of aggressive chordomas of the clival region. All of the parental tumors showed telomerase activity. Cultured chordoma cells had a doubling time of 5 to 7 days and grew as a monolayer of cells that retained both the immunophenotype and the p53 status of the parental tumor. In vitro, chordoma cells overexpressed telomerase, supporting the hypothesis that this enzyme is required for the immortalization process.

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Roberto Pallini, Francesco Pierconti, Maria Laura Falchetti, Daniela D'Arcangelo, Eduardo Fernandez, Giulio Maira, Ettore D'Ambrosio and Luigi Maria Larocca

Object. Evidence from recent in vitro studies indicates that reactivation of telomerase, the enzyme that synthesizes the telomere ends of chromosomes, is a crucial event in the unlimited clonal expansion of endothelial cells that precedes the neoplastic conversion of these cells. It is known that high-grade gliomas express telomerase and that, in these neoplasms, proliferating endothelial cells may undergo transformational changes with development of sarcomatous components within the primitive tumor. To assess whether telomerase is involved in the endothelial cell proliferation that characterizes brain tumor angiogenesis, the authors investigated at the single-cell level the expression of messenger (m)RNA for the human telomerase catalytic subunit human telomerase reverse transcriptase (hTERT) by vascular cells of astrocytic tumors.

Methods. The in situ hybridization (ISH) method was performed by processing histological sections with specific riboprobes for hTERT and for c-myc, an oncogene that is known to upregulate hTERT. Results of the ISH studies were compared with proliferative activity, as estimated by Ki-67 immunostaining. The expression of hTERT mRNA by vascular endothelial cells was related to the histological grade of the tumor because it was detected in five (29%) of 17 low-grade astrocytomas, nine (56%) of 16 anaplastic astrocytomas, and 19 (100%) of 19 glioblastomas multiforme (GBMs). Expression of c-myc mRNA was strictly correlated with that of hTERT mRNA. In low-grade astrocytomas and anaplastic astrocytomas, a dissociation was noted between hTERT mRNA expression and the proliferation rate of endothelial cells. Conversely, GBMs displayed a significant correlation between the level of hTERT mRNA expression and endothelial cell proliferation. Data from an in vitro assay in which human umbilical vein endothelial cells were stimulated to proliferate by adding vascular endothelial growth factor and an ISH study of newly formed vessels surrounding brain infarcts confirmed that expression of hTERT mRNA does not merely reflect the proliferative status of endothelial cells but represents a specific feature of brain tumor neovascularization.

Conclusions. The results of this study are consistent with a role of telomerase in the angiogenesis of astrocytic tumors. Expression of hTERT mRNA by tumor vascular cells is an early event during the progression of astrocytic tumors, which precedes endothelial cell proliferation and may represent a first sign of dedifferentiation. Other than elucidating the mechanisms of tumor angiogenesis, these results encourage research on antitelomerase drugs for the treatment of malignant gliomas.